Genome sequencing in persistently unsolved white matter disorders

Guy Helman; Bryan R. Lajoie; Joanna Crawford; Asako Takanohashi; Marzena Walkiewicz; Egor Dolzhenko; Andrew M. Gross; Vladimir G. Gainullin; Stephen J. Bent; Emma M. Jenkinson; Sacha Ferdinandusse; Hans R. Waterham; Imen Dorboz; Enrico Bertini; Noriko Miyake; Nicole I. Wolf; Truus E.M. Abbink; Susan M. Kirwin; Christina M. Tan; Grace M. Hobson; Long Guo; Shiro Ikegawa; Amy Pizzino; Johanna L. Schmidt; Genevieve Bernard; Raphael Schiffmann; Marjo S. van der Knaap; Cas Simons; Ryan J. Taft; Adeline Vanderver

doi:https://doi.org/10.1002/acn3.50957

Genome sequencing in persistently unsolved white matter disorders

Guy Helman, Bryan R. Lajoie, Joanna Crawford, Asako Takanohashi, Marzena Walkiewicz, Egor Dolzhenko, Andrew M. Gross, Vladimir G. Gainullin, Stephen J. Bent, Emma M. Jenkinson, Sacha Ferdinandusse, Hans R. Waterham, Imen Dorboz, Enrico Bertini, Noriko Miyake, Nicole I. Wolf, Truus E.M. Abbink, Susan M. Kirwin, Christina M. Tan, Grace M. HobsonLong Guo, Shiro Ikegawa, Amy Pizzino, Johanna L. Schmidt, Genevieve Bernard, Raphael Schiffmann, Marjo S. van der Knaap, Cas Simons, Ryan J. Taft, Adeline Vanderver

Research output: Contribution to journal › Article › Academic › peer-review

26 Citations (Scopus)

Abstract

Genetic white matter disorders have heterogeneous etiologies and overlapping clinical presentations. We performed a study of the diagnostic efficacy of genome sequencing in 41 unsolved cases with prior exome sequencing, resolving an additional 14 from an historical cohort (n = 191). Reanalysis in the context of novel disease-associated genes and improved variant curation and annotation resolved 64% of cases. The remaining diagnoses were directly attributable to genome sequencing, including cases with small and large copy number variants (CNVs) and variants in deep intronic and technically difficult regions. Genome sequencing, in combination with other methodologies, achieved a diagnostic yield of 85% in this retrospective cohort.

Original language	English
Pages (from-to)	144-152
Number of pages	9
Journal	Annals of Clinical and Translational Neurology
Volume	7
Issue number	1
Early online date	7 Jan 2020
DOIs	https://doi.org/10.1002/acn3.50957
Publication status	Published - Jan 2020

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Helman, G., Lajoie, B. R., Crawford, J., Takanohashi, A., Walkiewicz, M., Dolzhenko, E., Gross, A. M., Gainullin, V. G., Bent, S. J., Jenkinson, E. M., Ferdinandusse, S., Waterham, H. R., Dorboz, I., Bertini, E., Miyake, N., Wolf, N. I., Abbink, T. E. M., Kirwin, S. M., Tan, C. M., ... Vanderver, A. (2020). Genome sequencing in persistently unsolved white matter disorders. Annals of Clinical and Translational Neurology, 7(1), 144-152. https://doi.org/10.1002/acn3.50957

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title = "Genome sequencing in persistently unsolved white matter disorders",

abstract = "Genetic white matter disorders have heterogeneous etiologies and overlapping clinical presentations. We performed a study of the diagnostic efficacy of genome sequencing in 41 unsolved cases with prior exome sequencing, resolving an additional 14 from an historical cohort (n = 191). Reanalysis in the context of novel disease-associated genes and improved variant curation and annotation resolved 64% of cases. The remaining diagnoses were directly attributable to genome sequencing, including cases with small and large copy number variants (CNVs) and variants in deep intronic and technically difficult regions. Genome sequencing, in combination with other methodologies, achieved a diagnostic yield of 85% in this retrospective cohort.",

author = "Guy Helman and Lajoie, {Bryan R.} and Joanna Crawford and Asako Takanohashi and Marzena Walkiewicz and Egor Dolzhenko and Gross, {Andrew M.} and Gainullin, {Vladimir G.} and Bent, {Stephen J.} and Jenkinson, {Emma M.} and Sacha Ferdinandusse and Waterham, {Hans R.} and Imen Dorboz and Enrico Bertini and Noriko Miyake and Wolf, {Nicole I.} and Abbink, {Truus E.M.} and Kirwin, {Susan M.} and Tan, {Christina M.} and Hobson, {Grace M.} and Long Guo and Shiro Ikegawa and Amy Pizzino and Schmidt, {Johanna L.} and Genevieve Bernard and Raphael Schiffmann and {van der Knaap}, {Marjo S.} and Cas Simons and Taft, {Ryan J.} and Adeline Vanderver",

year = "2020",

month = jan,

doi = "https://doi.org/10.1002/acn3.50957",

language = "English",

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pages = "144--152",

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Helman, G, Lajoie, BR, Crawford, J, Takanohashi, A, Walkiewicz, M, Dolzhenko, E, Gross, AM, Gainullin, VG, Bent, SJ, Jenkinson, EM, Ferdinandusse, S , Waterham, HR, Dorboz, I, Bertini, E, Miyake, N, Wolf, NI , Abbink, TEM, Kirwin, SM, Tan, CM, Hobson, GM, Guo, L, Ikegawa, S, Pizzino, A, Schmidt, JL, Bernard, G, Schiffmann, R, van der Knaap, MS, Simons, C, Taft, RJ & Vanderver, A 2020, 'Genome sequencing in persistently unsolved white matter disorders', Annals of Clinical and Translational Neurology, vol. 7, no. 1, pp. 144-152. https://doi.org/10.1002/acn3.50957

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AU - Takanohashi, Asako

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AU - Dolzhenko, Egor

AU - Gross, Andrew M.

AU - Gainullin, Vladimir G.

AU - Bent, Stephen J.

AU - Jenkinson, Emma M.

AU - Ferdinandusse, Sacha

AU - Waterham, Hans R.

AU - Dorboz, Imen

AU - Bertini, Enrico

AU - Miyake, Noriko

AU - Wolf, Nicole I.

AU - Abbink, Truus E.M.

AU - Kirwin, Susan M.

AU - Tan, Christina M.

AU - Hobson, Grace M.

AU - Guo, Long

AU - Ikegawa, Shiro

AU - Pizzino, Amy

AU - Schmidt, Johanna L.

AU - Bernard, Genevieve

AU - Schiffmann, Raphael

AU - van der Knaap, Marjo S.

AU - Simons, Cas

AU - Taft, Ryan J.

AU - Vanderver, Adeline

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AB - Genetic white matter disorders have heterogeneous etiologies and overlapping clinical presentations. We performed a study of the diagnostic efficacy of genome sequencing in 41 unsolved cases with prior exome sequencing, resolving an additional 14 from an historical cohort (n = 191). Reanalysis in the context of novel disease-associated genes and improved variant curation and annotation resolved 64% of cases. The remaining diagnoses were directly attributable to genome sequencing, including cases with small and large copy number variants (CNVs) and variants in deep intronic and technically difficult regions. Genome sequencing, in combination with other methodologies, achieved a diagnostic yield of 85% in this retrospective cohort.

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Genome sequencing in persistently unsolved white matter disorders

Abstract

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